Halilectin-3, a Lectin from the Marine Sponge Haliclona caerulea, Induces Apoptosis and Autophagy in Human Breast Cancer MCF7 Cells Through Caspase-9 Pathway and LC3-II Protein Expression

Neto, Luiz Gonzaga do Nascimento; Cabral, M. Guadalupe; Carneiro, Rômulo Farias; Silva, Zélia; Arruda, Francisco Vassiliepe Sousa; Nagano, Celso Shiniti; Fernandes, Alexandra R.; Sampaio, Alexandre Holanda; Teixeira, Edson Holanda; Videira, Paula A.

doi:10.2174/1871520617666171114094847

Cited by 25 publications

(19 citation statements)

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“…LC3-II of 14 kD is located on the autophagosome membrane, and its content is proportional to the number of auto-phagosome vesicles, so LC3-II is one of the marker proteins of auto-phagosome formation [8]. LC3-II/LC3-I ratio is usually adopted to reflect the number of auto-phagosomes and the level of autophagy in cells [9]. Studies have found that PI3K I/Akt/ mTOR and PI3K III/Beclin-1/Bcl-2 are important signaling pathways involved in cell autophagy [10,11].…”

Section: Introductionmentioning

confidence: 99%

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

Zhang

Wang

et al. 2020

BMC Complement Med Ther

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Background: Germacrone is an anti-inflammatory ingredient in the Chinese medicine zedoary turmeric. The purpose of this study was to explore the protective mechanism of germacrone against PC12 cells injury caused by oxygen-glucose deprivation/reperfusion (OGD/R). Methods: OGD/R injury model of PC12 cells was established by using OGD/R (2 h/24 h). The cell viability was assessed by MTT assay and LDH release. The ultrastructure of cells was observed by transmission electron microscopy (TEM). The expression of autophagy related proteins in cells was determined by Western Blot. Results: The results of ultrastructural observation showed that PC12 cells damaged by OGD/R showed typical autophagy characteristics. In addition, OGD/R observably up-regulated the expression of autophagy related proteins: the class III type phosphoinositide 3-kinase (PI3K III), light chain 3(LC3), and Beclin-1 in PC12 cells, and inhibited the expression of the class I type phosphoinositide 3-kinase (PI3K I), Protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and B-cell lymphoma 2(Bcl-2) proteins. Furthermore, germacrone increased the cell viability of OGD/R-damaged PC12 cells by down-regulating the expression of LC3 protein in cells in a concentration-dependent manner. More importantly, germacrone significantly inhibited the expression of PI3K III, LC3, and Beclin-1 in OGD/R-injured PC12 cells, and up-regulated the expressionof PI3K I, Akt, mTOR, and Bcl-2 proteins in cells, and this inhibited or up-regulated effect was reversed by PI3K I inhibitor (ZSTK474). Conclusion: The above results indicated that germacrone could inhibit the autophagy effect in OGD/R injury model of PC12 cells, the mechanism of inhibition was regulated by PI3K III/Beclin-1/Bcl-2 and PI3K I/Akt/mTOR pathways, thereby improving the cell viability of PC12 cells and playing a neuroprotective role, which provided a new drug for the treatment of OGD/R.

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Section: Introductionmentioning

confidence: 99%

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

Zhang

Wang

et al. 2020

BMC Complement Med Ther

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“…High levels of caspase-3, caspase-9 and Bax/Bcl-2 indicate that cells are in a state of induced apoptosis. 25,26 It is reported that caspase-3 and Bax can respond to ganoderma lucidum spore oil in vitro and in vivo treatment of BC. The inactivated caspase-9 is related to the tumor survival of triple-negative BC, and Bcl-2 is a vital factor in the antiapoptosis defense mechanism of BC.…”

Section: Dovepressmentioning

confidence: 99%

<p>LncRNA DANCR-miR-758-3p-PAX6 Molecular Network Regulates Apoptosis and Autophagy of Breast Cancer Cells</p>

Zhang¹,

Li²,

Ding³

et al. 2020

CMAR

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Objective: This study set out to probe into the effects of long non-coding RNA (LncRNA) differentiation antagonizing non-protein coding RNA (DANCR) on apoptosis and autophagy of breast cancer (BC) cells. Methods: The expression levels of DANCR, miR-758-3p and paired box 6 (PAX6) in BC tissues and cell lines were detected. The transcription and protein levels of PAX6, apoptosisrelated factors (caspase-3, caspase-9, Bax/Bcl-2), and autophagy-related factors (LC3B, Atg5, Beclin-1) in BC cells were detected. The cell proliferation, apoptosis, autophagy and the regulatory relationship between genes and target genes were analyzed. Results: DANCR and PAX6 were up-regulated in BC tissues and cell lines, while miR-758-3p was opposite. Down-regulating DANCR inhibited the malignant proliferation of BC cells and also promoted apoptosis and autophagy, which showed that caspase-3, caspase-9, Bax/ Bcl-2, LC3B, Atg5 transcription and protein levels increased, while Beclin-1 transcription and protein levels decreased. DANCR regulated miR-758-3p in a targeted manner, and its over-expression could weaken the anti-cancer effect of miR-758-3p on BC cells. In addition, miR-758-3p also directly targeted PAX6, and knocking down its expression could weaken the inhibitory effect of down-regulating PAK6 on BC cell apoptosis and autophagy. We also found that DANCR acted as a competitive endogenous RNA sponge miR-758-3p, thus regulating the PAX6 expression. Conclusion: DANCR-miR-758-3p-PAX6 molecular network plays a key regulatory role in BC cell apoptosis and autophagy, which may provide reference for treating patients.

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“…In particular, H3 upregulated the microtubule-associated protein 1A/1B-light chain 3 (LC3) expression, promoting the accumulation of LC3-II (Table 2). Contextually, autophagosome vesicles have been identified microscopically [66]. The authors of the study [40] hypothesize that both apoptosis and autophagy can be triggered thanks to Bcl-2 downregulation or p53 upregulation.…”

Section: Phylum Poriferamentioning

confidence: 99%

“…The authors of the study [40] hypothesize that both apoptosis and autophagy can be triggered thanks to Bcl-2 downregulation or p53 upregulation. To complete the picture, H3 has been found able to promote anoikis, a particular form of cell death that happens when cells are stimulated to detach from the extracellular matrix [66]. In normal conditions, cells need to adhere to the tissue where they grow since the essential growth factors and other survival signals are provided by the extracellular matrix and proximal cells [88].…”

Section: Phylum Poriferamentioning

confidence: 99%

“…In normal conditions, cells need to adhere to the tissue where they grow since the essential growth factors and other survival signals are provided by the extracellular matrix and proximal cells [88]. H3 reduced the expression of integrin α6β1 and interacted with integrin α5β1, the fibronectin receptor, thus impairing MCF-7 adhesion and promoting cell death [66]. The involvement of apoptosis, autophagy, and anoikis in the cytotoxicity of H3 makes it a very promising antitumor lectin, able to fight cancer on several fronts and thus reduce drug resistance.…”

Section: Phylum Poriferamentioning

confidence: 99%

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Antitumor Potential of Marine and Freshwater Lectins

et al. 2019

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Often, even the most effective antineoplastic drugs currently used in clinic do not efficiently allow complete healing due to the related toxicity. The reason for the toxicity lies in the lack of selectivity for cancer cells of the vast majority of anticancer agents. Thus, the need for new potent anticancer compounds characterized by a better toxicological profile is compelling. Lectins belong to a particular class of non-immunogenic glycoproteins and have the characteristics to selectively bind specific sugar sequences on the surface of cells. This property is exploited to exclusively bind cancer cells and exert antitumor activity through the induction of different forms of regulated cell death and the inhibition of cancer cell proliferation. Thanks to the extraordinary biodiversity, marine environments represent a unique source of active natural compounds with anticancer potential. Several marine and freshwater organisms, ranging from the simplest alga to the most complex vertebrate, are amazingly enriched in these proteins. Remarkably, all studies gathered in this review show the impressive anticancer effect of each studied marine lectin combined with irrelevant toxicity in vitro and in vivo and pave the way to design clinical trials to assess the real antineoplastic potential of these promising proteins. It provides a concise and precise description of the experimental results, their interpretation as well as the experimental conclusions that can be drawn.

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Halilectin-3, a Lectin from the Marine Sponge Haliclona caerulea, Induces Apoptosis and Autophagy in Human Breast Cancer MCF7 Cells Through Caspase-9 Pathway and LC3-II Protein Expression

Abstract: The apoptotic effect of H3 may be related to a balance between apoptotic and autophagic cell death, mediated by increased expression of CASP 9 and LC3-II. To the best of our knowledge this is the first report about a sponge lectin triggering both apoptosis and autophagy in MCF7 cell.

Cited by 25 publications

References 0 publications

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

Germacrone protects against oxygen-glucose deprivation/reperfusion injury by inhibiting autophagy processes in PC12 cells

<p>LncRNA DANCR-miR-758-3p-PAX6 Molecular Network Regulates Apoptosis and Autophagy of Breast Cancer Cells</p>

Antitumor Potential of Marine and Freshwater Lectins

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